Horizontal gene transfer as a source of evolutionary innovation in metazoans Project summary Rotifers of the class Bdelloidea, microscopic freshwater invertebrates, are known for their long-term asexuality and extreme resistance to ionizing radiation, which may be a consequence of adaptation to frequent bouts of desiccation and rehydration in their natural ephemerally aquatic habitats. Previously, we discovered that bdelloids are also susceptible to massive horizontal gene transfer from diverse sources, including bacteria, fungi, plants, and protists. We have recently extended these findings to the genome-wide scale through analysis of the high-quality draft sequence of the bdelloid Adineta vaga, which revealed that as much as 8%, and likely even more, of its protein-coding genes are of foreign origin. We now propose to investigate the role that selected foreign genes might play in bdelloid genome function and evolutionary adaptation to changing environments. Functional studies of horizontally transferred genes, which are rare in metazoans, have so far been limited to studies of isolated enzymes performing a specific reaction, such as biosynthesis of a pigment, or decomposition of a compound. Here, we plan to take functional studies of metazoan horizontal transfers to a new level, and seek to investigate cases of horizontal transfer that may have resulted in major evolutionary innovations: acquisition of a non-canonical system of epigenetic modification differing from that in other eukaryotes; acquisition and unprecedented expansion of antibiotic resistance genes and emergence of regulatory systems controlling their expression; and acquisition and diversification of a versatile system of secondary metabolism that has the potential to yield a variety of novel bioactive compounds. Beyond adding significantly to our fundamental knowledge of the contribution of lateral gene transfer to metazoan evolution, these studies may eventually help in understanding the pathways to evolution of antibiotic resistance, and may further lead to discovery of previously unknown classes of secondary metabolites with unique biological or medicinal properties.